# Potential Involvement of PI3K/AKT Signaling Pathway in the Protective Effects of Rhinacanthus nasutus Against Diabetic Nephropathy-Induced Oxidative Stress

## TL;DR

This study shows that Rhinacanthus nasutus extract may protect against diabetic kidney damage by reducing oxidative stress and regulating glucose uptake.

## Contribution

The novel contribution is identifying Rhinacanthus nasutus as a potential natural treatment for diabetic nephropathy via the PI3K/AKT pathway.

## Key findings

- Rhinacanthus nasutus extract reduced oxidative stress markers in diabetic rats.
- The extract upregulated PI3K/AKT signaling and improved glucose uptake in cell assays.
- Bioavailable compounds like caffeic acid and naringenin were identified as key constituents.

## Abstract

Oxidative stress is a primary driver of diabetic nephropathy (DN), highlighting the urgent need for potent natural antioxidants. This study explored the reno-protective potential and associated mechanisms of Rhinacanthus nasutus aqueous extract (AE). Phytochemical profiling via Q Exactive HF Orbitrap LC–MS/MS and serum pharmacochemistry analysis identified 38 constituents, among which 25 bioavailable constituents (e.g., caffeic acid and naringenin) might be the key bioactive ones. In the L6 myotubes in vitro assays, AE (75 μg/mL) was observed to upregulate the PI3K/AKT and GLUT4 signaling cytokines, coinciding with enhanced glucose uptake, as confirmed by Western blot with insulin as a positive control. Furthermore, in STZ-induced DN rats, AE could reduce MDA levels (0.58 vs. 1.44 nmol/mgprot) and restore T-SOD, CAT, and GSH-Px levels (170.57, 51.93, 63.68 vs. 114.93, 40.84, 50.99 mgprot). The protective effects were accompanied by the modulation of PI3K/AKT/mTOR signaling axis. These findings suggest that AE exerts dual efficacy involving glucose uptake regulation and oxidative stress inhibition. Consequently, Rhinacanthus nasutus represents a promising natural antioxidant resource with potential for the management of DN.